CI-IRISTOPH GRUNDMXNN AND EHRENFRIED KORER
944
diamino-s-triazine ( I V ) , 11 g. (0.135 mole) of dimethylamine hydrochloride and 1.4 g. (0.010 mole) of zinc chloridc. The mixture was fused and maintained a t 220-240' for 1 hr. with stirring. After cooling, 70 ml. of cold water was addcrl and filtered. The filtrate was extracted nith 100 nil. of Skellysolve 1 1 which upon evaporation yielded 0.112 g . of material, m.p. 40.5-42". The material froiii two such runs was combined, dissolved in 75 ml. of Skellysolve A , iiisoluble material removed by filtration, and the solid was chromatographed on an alumina column. The column was eluted with pure Skellysolve A; 50-ml. fractions were taken. The materials obtained from the fourth and fifth eluates (m .p. 42-43') were combined and recrystallized from Skellysolve -4, m.p. 45-46', and a mixed melting point with an authentic sample was not depressed, m.p. 44.5-45.5'. 4,6-Di-( monomethylamino)-s-triazinefrom C,€i-Diamino2-methyl-s-triazine .-This compound was prepared by essentially the same procedure described by Thurston, m.p. 255-256 O .16 4,6-Diarnino-2-methoxyethyl-s-triazine (111, R' = CH2C € 1 2 0 C H 1 ) . - A solution of 10 g. (0.1 mole) of biguanide and
[COSTRIBUTIOS
Vol. '71)
9 g. (0.1 mole) of methyl acrylate in 150 ml. of absolute methanol were refluxed for 1.5 hr. On cooling, 7 g. of crude product, n1.p. 20L5-%0Yo, was obtained. .Lifter digesting this product with aqueous methanol a t steam-bath temperature for 0.5 hr., insoluble material was removed b y filtration and tile solution cooled. Crystalline material, 6.5 g., was obtained, melting a t 21C-21I0. Conceiitration of tlie original filtrate yielded another 2 g. of product; total yield, 8.5 g. (5176). Annl. Calcd. for C6FIIINiO: C, 42.59; H, (5.65; N, 41.40; 0 , 9.46. Found: C, 42.58; €I, 6.49; N, 41.32; 0, 9.61.
Acknowledgments-lye wish to gratefully acknowledge the support of this work by a Grant-inaid from Eli Lilly and Company. We also thank the ilmerican Cyanamid Company for their generous gifts of phenylbiguanide and biguanitle. BROOKLYN 1. NEXV
FROM T H E OHIO S T A T E U N I V E R S I T Y
YORK
RESEARCH FOUNDATION]
Triazines. XVIII. The Reaction of Aliphatic Diazocompounds with ChIoro-s-triazines BY CI-IRISTOPH GRUNDMANN AND EHRENFRIED KOBER RECEIVED JURE 6,1956 Di- and trichloro-s-triazines react with diazomethane and its homologs to yield a-diazoalkyl-substituted triazines. Usually only one chlorine atom is substituted. The other chlorine atoms can be replaced by alkoxy- or amino groups without affecting the diazo group. On the basis of the reactivity of the diazo group toward halogens and acids, the a-diazoalkyl-striazines resemble derivatives of diazoacetic acid.
In many of their properties the cyanuric trihalides, or 2,4,6-trihalogeno-l,3,5-triazines, resemble the halogenides of organic acids. Because the latter compounds react easily with diazomethane and its homologs to give diazoketones, a reaction of halogeno-triazines and aliphatic diazo compounds seemed possible. Cyanuric chloride (I) reacts readily with two moles of diazomethane in ethereal solution a t room temperature, liberating elementary nitrogen to form a well crystallized yellow compound, 2-diazomethyl-4,6-dichloro-1,3,5-triazine (11). The possible isomeric structures of a triazolo-triazine (IIIa and IIIb) seem to be definitely excluded by the reactions of I1 which are quite analogous to those of the known aliphatic diazo compounds. Furthermore the infrared spectrum of this and other diazosubstituted triazines displays the characteristic band (at 2120 cm.-l) of the aliphatic diazo compounds. With a large excess of diazomethane and prolonged reaction time, the second chlorine atom of the cyanuric chloride also is substituted to some extent. Because of its instability, however, we were unable to prepare t.he expected 2,4-bis-diaxomethyl-6-chloro-triazine (IV) in a pure state. There was never any indication of the reaction of the third chlorine atom of I. Other chloro-s-triazines which react as well with diazomethane as does cyanuric chloride are 4,6( 1 ) This article is based on work performed under Project 116-B of T h e Ohio S t a t e University Research Foundation sponsored by t h e Olin Mathieson Chemical Corporation, h'ew York, N. Y .
(2) Preceding communication, Ch. Grundmann and E. Kober,
J - Org. Chem.. 21, 1392 (1956).
dichloro-2-methyl-s-triazine (V) and 4,6-dichloro2-phenyl-s-triazine (VI). They give the expected compounds, 6-chloro-4-diazornethyl-2-methyl-s-triazine (VII) and 6-chloro-4-diazomethyl-2-phenyl-striazine (VIII). 6-Chloro-2,4-diphenyl-s-triazine (IX) does not react. With 2,4-bis-trichloromethyl6-chloro-s-triazine3 (X), in which the chlorine attached to the nucleus is much more mobile than in IX, the reaction apparently is not only confined to the 6-position but also includes the trichloromethyl groups, thus complicating the picture. On the other hand, diazomethane can be replaced by homologs. For instance, from I and diazoethane 2 , l '-diazoethyl-4,6-dichloro-s-triazine (XI) is obtained; ethyl diazoacetate yields 4,6dichloro-s-triazinyl-2-diazoacetic acid ethyl ester (XII). The latter reaction requires elevated temperatures and prolonged reaction time, illustrating the lower degree of reactivity of the diazoester cornpared to the diazoalkanes. I t isnot surprising, then, that the more stable diazoketones, like w-diazoacetophenone, do not react with cyanuric chloride. The chlorine atoms in the 4- and 6-positions of the diazomethyl substituted triazines can be replaced without alteration of the diazo group by alkoxy groups, by thioalkyl groups and by amino groups. Using this method, 2-diazomethyl-4,6dimethoxy-s-triazine (XIII) and 2-diazomethyl-4,6-diethoxy-s-triazine (XIV) were prepared. Since the presence of the reactive chlorine atoms in the original reaction products, such as 11, often involves complications, many of the reactions of thc (3) H Schroeder and C h Grundmann, THISJ O D R N A L , 7 8 , 2447 (11)66).
ALIPHATICDIAZOCOMPOUNDS WITH CHLORO-S-TRIAZINES
Feb. 20, 19.57 diazo-substituted
triazines
were studied
with
945
reactivity of these compounds, however, is not as
2-diazomethyl-4,6-dimethoxy-s-triazine (XIII), great as that of the true diazoalkanes. Instead, they are comparable to the a-diazocarbonyl compounds. In fact, the a-diazoalkyltriazine derivatives structurally resemble the carbonyl compounds when one considers the valency state of the carbon atom attached to the C=N2 group. For example, the diazomethyltriazines may be considered as cyclic substituted amidines of diazoacetic acid. The reaction mechanism can thus be supposed to follow a course sitnilar to that suggested by Huisgen5 for the acyl chloride^.^ A diazo alkyl group, once formed, will tend to shift electrons into the triazine ring system and decrease the tendency of the C=N double bonds toward addition. I t is therefore understandable that a second chlorine atom in the 4-position does not react as easily, especially if another electrondonating group is already present in the 6-position. Obviously the C=N bond of the triazine ring will not become activated if two strong electron donors are present in the 2- and 4-positions. This explains the inertness of such 6-chlorotriazines as I X against diazomethane. CHARTI The diazomethyl-s-triazines react normally a t FORMATION OF DIAZOALKYL-S-TRIAZINES AND REACTIONS room temperature with halogens in an inert solvent NOT INVOLVING THE DIAZOGROUP like tetrachloromethane to give the expected diiYzCH( N y C N ~ Cl/"Cl RfN\12 halomethyl-s-triazines. A number of these compounds are presented in Table I . Ethereal hydrogen chloride converts the diazoS y N N\/x methyl-s-triazines into the corresponding chloroN cy1 N R cI1 methyl compounds. However, in each case etherIV I, R = C1 IX, R CoH5 insoluble by-products, the hydrochlorides of the X, R = CCL corresponding chloromethyl-s-triazines, are obV, R = CH3 VI, R = CsHs tained. If the starting material contains constituents attackable by hydrogen chloride, they too may be converted. For example, from XI11 R' we isolated the hydrochloride of 2-chloromethyl4,6-dihydroxy-s-triazine(XXIX), which indicates the cleavage of the two methoxy groups. The chlorine in the chloromethyl group is much less mobile than that directly bound to the triazine I I I ring. From 2-chloromethyl-4,6-dichloro-s-triazine c1 c1 c1 (XXVII), using alcoholic ammonia, we obtained IIIa IIIb only the 2-chloromethyl-4,6-diamino-s-triazine 11.R = C1: R ' = H (XXXIV) and, using sodium methoxide, 2-chloroVII; k = C H 3 ; R ' =-H methyl-4,6-dimethoxy-s-triazine (XXVIII) was obVIII, R = C6H5; R' = H XI, R = C1; R ' = CH3 tained; cf. Table 11, footnote b.
which reacts more uniformly. With methyl, ethyl and phenyl mercaptans the corresponding 4,6-substituted 2-diazomethyltriazines XV, XVI and XVII were obtained from 11, but only when the exact stoichiometric amount of the mercaptan was employed. Amino derivatives prepared from I1 include 4amino-6-chloro-2-diazomethyl-s-triazine (XVIII ) , 4,6-diamino-2-diazomethyl-s-triazine (XIX),6-chloro-2-diazomethyl-4-diethylamino-s-triazine (XX), 4,6-bis-diethylamino-2-diazomethyl-s-triazine (XX I ) and 4,6-aziridino-2-diazomethyl-s-triazine (XX I I ) . A naturally occurring aliphatic diazo compound, 0-diazoacetyl- I - serine (azaserine), has among its interesting properties a marked cytostatic a ~ t i v i t y . Compounds ~ of type X X I I may be of certain interest in this respect since they contain the active ethylene-imino group and the aliphatic diazo group in the same molecule. The reactions discussed above are summarized in Chart I.
-
!I I
X I I , R = C1; R ' = COOEt
I
CHzCl
CHzCl
I
I
3
X/\N
I1
Cl\ II
I
J-Cl
N XXVII
N/\N
/I
--f
R-(,J-R
I
XXVIII, R = OCH3 XXXIV, R NHz
Dilute sulfuric acid converts the diazomethyl-striazines to the corresponding primary carbinols, X I I I , R ' = OCHs XVIII, R = C1; R ' = HP whereas organic acids lead to good yields of the OCzHs X I X , R = NHz; R' = HZ XIV, R' corresponding esters. A number of compounds obXV. R ' = S-CHI XX. R = C1: R' = (C2H5h XVI; R' = s-c9H6 XXI; R = (c;H&N; Xi = ' ( c ~ H ~ )tained ~ by the action of acids on the diazomethyl-sXVII, R ' = S-CBHS X X I I , R = (CH2)zN; R' = (CH2)z triazines are presented in Table 11. The diazo group in all the a-diazoalkyltriazine Acknowledgment.-We are very much indebted derivatives investigated undergoes the reactions to the Olin Mathieson Chemical Corporation for characteristic of aliphatic diazo compounds. The their generous support of this work. We furtherR'
R
(4) S. Fusari, et al., THISJOURNAL, 76, 2878, 2881 (1954).
(5)
Cf.R . Huisgen, Angew. C k e m . , 67, 439
(1955).
CIIRISTOPII GRUNDMANN AND EIIRENFRIED KOBER
946
TABLE I DIHALOGESOMETHY L-S-TRIAZINES R
R
R
R
B.P.
R
Yield,
"C.
Mm.
c1
78-82
0.05
c1
89-9 1" 86-88
No.
X
XXIII
c1
XXIV XXV
I C1
OCHs
Vol. 79
nln
I , OC.
%
1.5550
25
72.0
23
89.5 33.4
.... ,045 1.5200
XXVI Br OCHs 112-113 ,017 1.5628 27 71.2 M.p.; XXIV decomposes gradually a t room temperature 61.19.
Formula
-FoundC
H
N
C4HClrNS
20.93 0.76 17.63 C1, 60.52 CrHClJzKc'3 C1, 18.40 CsH1ClzNo02 32.32 3.2G 19.10 C1, 31.25 CBH7Br2N802Br, 51.03 under liberation of iodine. Found:
--Calcd.---C
H
N
20.63 0 . 4 3 18.01 C1, G O . 90 C1, 17.10 32.16 3.15 18.70 C1, 31.65 Br, 51.07 I, 56.48. Calcd.: I,
TABLE I1 FROM DIAZOMETHYL-S-TRIAZINES A N D ACIDS REACTION PRODUCTS R R
\=g I
I
R R CI OCH: OH xxx OH OCHi XXXI OCHn OOCCHi XXXII OOCCsHr OCHi XXXIII OOCCaH4NHi(p) N( CzHd t
NO.
XXVII c1 XXVIII CI c1 XXIX
X
R M,.p.,
c.
36-37a 58-58.5 218-22OC 115-116 44.5-45.5 84-86 88-89
Yield,
%
76 27b 70d 57 74 81 88
Formula C C I H X C ~ ~ N : 24.19 CsHsClNaOn 3 7 . 9 8 C4HaClrNsOr 2 3 . 9 7 41.99 CsHoNaOi 44.99 CaHiiNi01 56.86 CirHirNaOi 61.08 CioHmNsOs
Found H N 1.29 21.58 4.39 22.11 3.48 20.89 5.27 24.54 5.26 19.71 4.71 15.15 7.68 22.58
.--
CI 53.08 18.58 35.62
C 24.21 38.01 24.24 42.10 45.06 56.42 61.26
C a 1 c d . p H N C e 1.01 2 1 . 1 8 53.60 4.25 22.16 18.70 2 . 5 5 21.23 35.81 5.30 24.55 5.20 19.71 4.76 15.27 7 . 5 8 22.57
Allotropic form melts a t 20.5'; b.p. 70-71' (0.05 mm.), ?Zs.6D 1.5461. XXVIII was also obtained with 92% yield Isolated as the hydrochloride from from XXVII by refluxing with two moles of sodium methoxide in methanol for 2 hr. Crude product, see Experimental part. XI11 and HC1, besides XXVIII.
more appreciate a gift of cyanuric chloride from Nilok Chemicals, Inc., Lockport, N. Y.
ExperimentalaJ 2-Diazomethyl-4,6-dichloro-s-triazine(II).-A
solution of 44.3 g. of pure cyanuric chloride in 800 ml. of ether was slowly added with stirring t o a solution, held at O n , of approximately 23 g. of diazomethane in 1000 ml. of ether. The reaction mixture was allowed t o stand for two days a t room temperature and then filtered from a small amount of solid by-products. The ether was removed from the filtrate by distillation at room temperature under a slight vacuum. The resulting residue was extracted three times with 800, 500 and, finally, 300 ml. of hot ligroin.8 After maintaining the extracts at a temperature of -25' for two days; yellow starlets crystallized (39.7 g., 87.5y0), m.p. 110-111 . This product was sufficiently pure for most purposes. For final purification the crystals were sublimed in small amounts, under atmospheric pressure at 100-125', yielding faint yellow, thin needles, m.p. 111.5-112.5'. Anal. Calcd. for C,HClnN,: C, 25.29; H , 0.53; C1, 37.32; N, 36.86. Found: C, 25.33; H , 0.59; C1, 37.01; N, 36.70. 2,4-Bis-diazomethy1-6-chloro-s-triazine(IV).-This compound was formed from the above described reaction by (6) All melting points were taken with the Fisher-Johns apparatus; microanalyses were by the Galbraith Laboratories, Knoxvillle, Tenn., and Spang Microanalytical Laboratory, Ann Arbor, Michigan. (7) Care is recommended in working with large amounts of all these diazo compounds. All of them decompose rapidly when overheated, and in some cases, the decomposition was followed by a violent explosion. Crude material is usually more sensitive than purified. Whenever possible, it is recommended first t o recrystallize before sublimation or distillation of these compounds. (8) If not indicated otherwise, a fraction with a boiling range from 90-97O was used in this and the following experiments.
using only one-third as much cyanuric chloride and allowing the reaction mixture to stand for seven days. Yellow crystals (0.8 g., m.p. 92-120" dec.) separated only from the first ligroin extract. Analysis revealed that these crystals were a mixture of approximately 50y0 of the monodiazomethyl compound I1 and the desired IV. Separation of this mixture by means of recrystallization or sublimation failed because the bis-diazo compound IV invariably decomposed during these operations with evolution of nitrogen. Anal. Calcd. for a mixture of 50% CrHClzNb and 50% of C ~ H ~ C I N TC,: 28.00; H , 0.78; C1, 27.72; N, 43.50. Found: C,28.71; H, 1.55; C1,26.68; N,42.81.
6-Chloro-4-diazomethyl-2-methyl-s-triazie(VII).--A solution of 24.6 g. of 4,6-dichloro-2-methyl-s-triazineein 700 ml. of dry ether was slowly added with stirring to the solution of 14 g. of diazomethane in 600 ml. of dry ether a t 0". After standing for two days a t room temperature, the solid by-products which formed were filtered off, the ether and excess diazomethane were removed by distillation and the resulting residue was extracted with 500 ml. of ligroin a t room temperature. The extract was kept a t -25' for several days, whereupon a small amount of a yellow crystalline by-product precipitated, which was removed by filtration. After the filtrate was concentrated in OUCUO to about 200 ml., a mixture of yellow needles and starlets crystallized upon storage a t -25'. The crystals were filtered off and the needles and starlets separated by hand. The starlets proved to be unchanged starting material, while the needles (0.8 9.) were the desired diazo compound VII. After recrystallization from ligroin, very thin yellow needles were obtained, m.p. 89-90 ' Anal. Calcd. for C ~ H I C ~ NC, ~ : 35.41; H, 2.37; C1, 20.91. Found: C,35.38; H,2.27; C1,21.13.
.
(9) W. Hentrich and M. Hardtmann, U. S. Patent 1,991,689.
ALIPHATICDIAZOCOMPOUNDS WITH CHLORO-S-TRIAZINES
Feb. 20, 1957
6-Chlor~4-diazomethyl-2-phenyl-s-triazine (MI).-Essentially the same procedure as described for I1 produced the diazotriazine VI11 (8.85 g., 76.3y0) from 11.3 g. of 4,6dichlor0-2-phenyl-s-triazine~~in 700 ml. of ether and 11.5 g. of diazomethane in 500 ml. of ether. !I11 crystallized from ligroin as yellow starlets, m.p. 107-109 Anal. Calcd. for C ~ O H B C I NC, ~ : 51.85; H, 2.61; C1, 15.31; N, 30.24. Found: C, 52.11; H, 2.90; C1, 15.01; N,29.80. 2 [ 1'-Diazoethyl]-4,6-dichloro-s-triazine(=).-The reaction between cyanuric chloride (18.45 g.) and diazoethane (about 0.3 mole) was carried out essentially as described above for the preparation of 11. The oily residue remaining after distilling off the ether was extracted twice, once with 750 and then with 500 ml. of boiling ligroin. After standing for one day a t -20', a yellow oil containing some crystals had separated from the extracts. The supernatant liquid was separated by decantation and evaporated an vacuo to a small volume. The diazotriazine X I (2.45 g.) crystallized in orange colored needles, m.p. 97-100', after drying on a porous clay plate. From the aforementioned oil a further crop of 1.1 g. of X I was obtained by extraction with ligroin followed by treatment of this extract as described before; yellow needles, m.p. 100-101 ', crystallized from ligroin. Anal. Calcd. for C5H8C12Ns: C, 29.43; H , 1.48; N, 34.33; C1, 34.76. Found: C, 29.06; H, 1.73; N, 33.80; C1, 35.46. (4,6-Dichloro-s-triazinyl-2)-diazoacetic Acid Ethylester (XII).-A mixture of ethyl diazoacetate (0.066 mole) and cyanuric chloride (0.01 mole) in 40 ml. of ligroin was refluxed for 9 hr. After distilling off the solvent, the excess diazoacetate and the formed ethyl chloroacetate were removed i n vacuo, raising the bath temperature gradually to 135' a t 3.5 mm. A red oil remained which, after standing for several days at room temperature, partially crystallized. The crystals were dried on a porous clay plate. After several recrystallizations from ligroin, yellow needles (0.68 g.), m.p. 53-54', were obtained. Anal. Calcd. for C7H5C12N502: C, 32.08; H , 1.92; C1, 27.06; N, 26.73. Found: C, 32.39; H, 1.94; C1, 27.00; N , 26.53. 2-Diazomethyl-4,6-dimethoxy-s-triazine (XIII).-A solution of 38 g. of 2-diazomethyl-4,6-dichloro-s-triazine (11) in 650 ml. of methanol was added slowly with stirring to a solution of 9.2 g. of sodium in 250 ml. of methanol a t 0'. After standing for 24 hr., the reaction was completed by refluxing for 30 minutes. The formed sodium chloride was filtered off and the methanol removed from the filtrate by distillation, applying a slight vacuum a t the end of the operation. The resulting residue was extracted with boiling ligroin (b.p. 60-70'), from which the diazotriazine XI11 separated as yellow prisms (28.3 g., 78.4%) on cooling. The product could be further purified by zacuum sublimation ( 110-135' (0.015 mm.)), m.p. 105-106 Anal. Calcd. for CeH,NrO,: C, 39.78; H , 3.89; N, 38.67. Found: C,39.82; H , 3.90; N, 38.94. I n an analogous manner, I1 was converted by sodium ethylate in ethanol with 70% yield into 2-diazomethyl-4,6diethoxy-s-triazine (XIV); yellow prisms, m.p. 62.5', were obtained from ligroin (b.p. 60-70'). Anal. Calcd. for C ~ H I I N ~ O ZC,: 45.93; H , 5.30; N, 33.48. Found: C, 46.07; H , 5.30; N,33.36. 4,6-Bis-thiomethyl-2-diazomethyl-s-triazine(XV).-Sodium (1.15 9.) was dissolved in 50 g. of methanethiol with stirring a t a temperature between -20 and 0'. The excess of methanethiol was allowed t o evaporate a t room temperature and the solid residue suspended in 100 ml. of xylene, cooled to 0" and 4.75 g. of finely powdered I1 added with stirring. The reaction mixture was stirred for 10 hr. a t room temperature and finally kept for 30 minutes between 50 and 60". All operations were carried out under pure nitrogen. After filtering, the filtrate was freed from xylene by distillation in a vacuum a t 50" bath temperature. The residue crystallized from ligroin in thin yellow needles (3.75 g., 70%) which soon turned violet on exposure t o light; m.p. 112-115'.
.
.
, 738 (1912); R. Hirt, H. Ni( 1 0 ) A. Ostrogovich, Chem. Z ~ K .36, decker and E. Berchtold, Helu. Chim. Acta, 33, 1365 (1950).
947
Anal. Calcd. for C&N&: C, 33.79; H , 3.30; N, 32.84; S, 30.07. Found: C, 33.54; H , 3.10; N, 33.26; S, 30.14. In an analogous manner, using ethanethiol instead of methanethiol, 4,6-bis-thioethyl-2-diazomethyl-s-triazine (XVI) was obtained from 11. The crude XVI remained as an orange colored oil, solidifying a t 0" after distilling off the xylene. The compound could be recrystallized from petroleum ether (b.p. 30-40'), m.p. 34-35'. Anal. Calcd. for C*HllhT&: C, 39.81; H , 4.60; N, 29.03. Found: C, 39.82; H,4.12; N,28.88. 4,6-Bis-thiophenyl-2-diazomethyl-s-triazine (XVII).-A solution of sodium (1.15 g.) in benzenethiol (85 g.) was prepared by refluxing with stirring in an atmosphere of nitrogen. The excess of solvent was removed by vacuum distillation. After cooling, the solid residue was allowed to react as described before with 4.75 g. of 11. The crude XVII (7.0 g., 83y0)crystallized from ligroin in yellow needles, sensitive to light, m a p .98-99'. Anal. Calcd. for CleH1IN&: C, 56.95; H , 3.29; N, 20.76; S, 19.00. Found: C, 56.86; H , 3.48; N, 20.73; s, 19.00. 4-Amino-6-chloro-2-diazomethyl-s-triazine(XVIII).Ammonia was passed for 2 hr. through a refluxing solution of 4 g. of 2-diazomethyl-4,6-dichloro-s-triazine (11) in 100 ml. of dry acetonitrile. After cooling down t o room temperature, the solution was filtered from the ammonium chloride and evaporated in ZJUCUO to dryness. The solid residue (2.4 g.) was extracted with ether, the combined ethereal extracts washed three times with water and dried over sodium sulfate. After removal of the ether in vacuo there remained 1.7 g. (60.870) of 2-amino-6-chloro-2-diazomethyl-s-triazine.By recrystallization from ligroin a yellowish micro-crystallme powder was obtained, m.p. 186' dec. Anal. Calcd. for CdHaClNe: C, 28.17; H, 1.75; C1, 20.79; N, 49.29. Found: C, 28.54; H, 1.80; C1, 20.33; N, 49.19. 4,6-Diamino-2-diazomethyl-s-triazine(XIX).-Several attempts t o prepare X I X either from XVIII or from I1 directly failed because the last chlorine atom was very difficult to replace by ammonia without alteration of the diazo group. T o prevent decomposition of the diazo group it is essential to have free ammonium hydroxide present as long as the crude X I X still contains ammonium chloride. The following procedure yielded an approximately pure product: A mGture of about 70 ml. of liquid ammonia and 4.75 g. of 2,4-dichloro-6-diazomethyl-l,3,5-triazinewas kept a t 60' for 8 hr. in an autoclave of 200 ml. volume. After the excess ammonia was allowed to evaporate, the reaction mixture was removed from the autoclave with ice-cold concentrated ammonium hydr6xide and filtered off by vacuum. The crude 4,6-diamino-2-diazomethyl-1,3,5-triazine(3.1 g., 82%), which still contained a considerable amount of ammonium chloride, was digested several times with aqueous ammonium hydroxide and the resulting paste dried on a porous plate. T o remove the last traces of ammonium chloride, X I X was heated for about one minute with a mixture of 50 ml. of ethyl alcohol, 25 ml. of water and 3 ml. of concentrated ammonium hydroxide and then filtered. The filter cake was extracted with ether and the remaining slightly colored powder dried over potassium hydroxide. The 4,6-diamino-2-diazomethyl-l,3,btriazineis practically insoluble in the usual solvents a t temperatures which do not cause decomposition of the diazo group. Heated under usual conditions, X I X decomposed gradually above 230'. On the Fisher- Johns apparatus a few crystals melted before decomposing when the plate was preheated to 240'. Anal. Calcd. for C ~ H S N TC, : 31.79; H, 3.34; N, 64.87. Found: C,31.82; H , 4.18; N,64.10. 4,6-Bis-diethylamino-2-diazomethyl-s-triazine(=).An amount of 4.75 g. of 2-diazomethyl-4,6-dichloro-striazine (11) in 200 ml. of ligroin (b.p. 60-70') was added a t 0" to diethylamine (20 g.) dissolved in 100 ml. of the same solvent and then the reaction mixture refluxed for 2 hr. The precipitated salts were filtered off and the filtrate was washed several times with water, dried over potassium carbonate and the solvent removed by distillation. The desired compound X X I remained as a yellow oil (5.45 g., 83%). I t could be purified by vacuum distillation, b.p. 110-115' (0.035 mm.).
948
SCOTT S E A R L E S , JR.,
KENNETH -1.POLLARTAND EUGENE F.LUTZ
Vol. '79
A n a l . Calcd. for C121321Si: C, 54.73; H, 8.04. Found: X X I X was characterized by coupling i t in alkaline solution C, 54.38; H, 8.12. with 8-naphthol in 907, yield t o the 4,6-dihydroxy-2-[2'naphthoxymethyl]-s-triazine. After recrystallization from Ulien the reaction was carried out with only two moles of diethylamine in ether at room temperature and worked up acetic acid, glistening leaflets were obtained, m.p. 300' dec. after 24 hr., the substitution was limited to one chlorine A t i d . Calcd. for C14HllN303:C , 62.45; H , 4.11; N, atom, resulting in 6-chloro-2-diazometh_yl-4-diethylamino-s- 15.61. Found: C, 62.45, 62.36; €1, 4.08, 4.16; S,1 5 . 3 , triazine (XX). Yellow prisms (4.5 g., 19%) were obtained 15.62. from ligroin, m.p. 52.5'. Anal. Calcd. for C8HIlClKe: The conversion of XI11 into the carbinol XXX occurred C, 42.39; H, 4.89; C1, 15.64; K, 37.08. Found: C, 42.23; spontaneously with evolution of heat when 4.75 g. of XI11 H , 4.93; C1, 14.91; N, 37.07. 4,6-Bis-ethyleneimino-2-diazomethyl-s-triazine(XXII) was suspended in 50 ml. of xvater and 0.6 g. of coned. sulfuric acid was added. After all had gone into solution, the was obtained in 527, yield by reaction of I1 with etliyleneimine (two moles) and triethylamine (two moles) in boiling carbinol was extracted five times with ether, the combined ether in an analogous manner. Recrystallizat.ion from ethereal extracts evaporated and the solid residue recrysligroin (b.p. 60-70') yielded a ycllow powder, which de- tallized from ligroin. The diazomethyltriaziries in general reacted much more easily with organic acids in the presence composed a t 108" ivithout melting. a small amount of water. Thus the conversion of XI11 Anal. Calcd. for CaH&7: C, 47.28; II, 4.47. Found: of into the acetate X X X I was best effected with 'JOYo acetic C, 47.32; H , 4.52. acid. The spontaneous reaction was completed by refluxing Conversion of the Diazomethyl-s-triazines into the Dihalo- for 10 minutes. After diluting with much water and neugenomethyl-s-triazines.--The finely powdered diazo com- tralizing with sodium bicarbonate, X X X I was extracted pound (I1 resp. XIII) was suspended in carbon tetrachloride with ether. The residue remaining after evaporation of containing one mole of the required halogen and kept at room the ether was recrystallized from ligroin. The reaction of temperature with stirring for 24 hr. If the halogen had not XI11 and X X I with the aromatic acids w-as carried out in yet reacted completely, the reaction mixture was then re- xylene with an excess of the acid and addition of about 1'; fluxed for 2-3 hr., filtered from solid by-products and the of water. After refluxing for 3-4 hr., the reaction mixture solvent removed by distillation. The residue was frac- was diluted with ether and the excess acid extracted with tionated twice under vacuum. In the case of the di-iodo sodium bicarbonate solution. The solvents were then rcderivative XXIV, which decomposes on heating, the crude moved by distillation, the last of the xylene being removrtl product was recrystallized from ligroin. Data of the in- under vacuum. The residue was recrystallizcd from ligroin, dividual compounds are compiled in Table I. in the case of X X X I I I preferably by seeding. Physical Reaction of the 2-Diazomethyl-s-triazines with Acids.and analytical data for the above compounds are compiled The diazomethyltriaziiies I1 and XI11 were dissolved in in Table 11. ether and an excess of hydrogen chloride passed in, followed Z-Chloromethyl-4,6-diamino-s-triazine (XXXIV).--A sat uby refluxing for 3 hr. After filtering off the insoluble hydro- rated solution of ammonia in ethanol (25 ml.) was added chlorides and evaporating the ether, the products XXVII dropwise a t 0" to a solution of 3.2 g. of 2-chloromethyl-4,0and XXVIII were isolated by vacuum distillation or recrys- dichloro-s-triazine (XXVII) in 3 ml. of anhydrous ether. tallization from ligroin. The amount of the insoluble hydro- The yellowish precipitate was collected and recrystallized chlorides could be considerably increased if the treatment twice from 20 ml. of water with addition of charcoal to give with hydrochloric acid was extended for two days. For white needles (1.7 g., 66%). The substan:e XXXIV darkexample, from 12.6 g. of 2-diazomethyl-4,6-dimethoxy-s- ened above 220" but did not melt up to 330 . triazine ( X I I I ) in 1500 ml. of pure anhydrous ether, we ob.lnal. Calcd. for CrI-I&l?i,: C, 30.11; €1, 3.79; C1, tained 10.1 g. of the crude hydrochloride of 2-chloromethyl4,6-dihydroxy-s-triazine(XXIX)(found: -2T, 21.12, 21.25; 22.21; N, 43.89. Found: C, 30.81; H , 3.83; C1, 21.84; C1, 36.02, 36.13). From the mother liquor another crop s,43.37. (0.6 g : ) of X X I X deposited after standing overnight (for COLUXBUS. OHIO analysis rf. Table TI).
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DEPARTMENT O F CHEMISTRY, KANSAS STATE COLLEGE]
Oxetanes. V1.l
Reductive Cleavage and Substituent Effects' B Y SCOTT SEARLES, JR., KENNETH A.POLLART AND EUGENE F. LUTZ RECEIVED AUGUST3, 1956
Reductive cleavage of ten oxetanes, having two or fewer alkyl substitucnt,s, has been carried out with lithium a l u ~ n i nun1 hydride and that of 2-phenyloxetane, with lithium borohydride. h single alcohol product was formed in cach case, cleavage of unsymmetrical oxetanes occurring between the oxygen atom and the least substituted a-carbon atom. The ease of cleavage was found to be much affected by substitution, particularly gem-dialkyl substitution at position 3 , which caused marked deactivation. These substituent effects are discussed. The preparations of 2-phenyloxetaxxe and 3-xneLhy~oxetane are described for the first time.
T H I S JOURNAL,
~ s e d ,and ~ , its ~ extension to oxetanes was suggested by the fairly high degree of reactivity observed for trimethylene oxide in Grignard reactions and in other reactions.' The smooth cleavage of triniethyletle oxide with lithium aluminum hydride, forming n-propyl alcohol, was reported in a preliminary fashion several
t h e degree Doctor of Philosophy in Chemistry a t Kansas State College.
(3) Lithium aluminnm hydride reductions are reviewed h y W €3 Ihown in hdanis' ''Organic Reactions," Vol. V I , J o h n \Vlley and Sons, Inc., Piew York, pi. Y., 1061, p . 476. ( 4 ) R I . S. Newman, G. Underwood and &I. Renoll, T H I S J U U K N A I . . 71, 3362 (1949).
Reductive cleavage of the oxetane (trimethylene oxide) ring would be of obvious value in establishing the structure of new oxetanes, as well as in certain synthetic applications. Reductive cleavage of 1,2-epoxides has been very widely and successfully (1) Earlier papers considered t o be in this series are: (a) S.Searles, 73, 124 (1951); (b) 4515 (1951); (c) S. Searles and C . 1'. Butler. ihid.. 76, 56 (1954); (d) S. Searles, i b i d . . 2313 (1954); S. Searles a n d V . 1'. Gregory, ibid.. 2789 (1954). (2) Portions of t h e dissertations presented by K . A . P. (1956) and t o be presented b y E. F. L. in partial fulfillment of t h e requirement for
